Targeted morpholino ligands and uses thereof

Abstract

Morpholino ligands that have high specificity for targets, such as proteins, and that bind their targets through non Watson-Crick base pairing, are described. The use of such morpholino ligands for targeted delivery of loads, such as drugs or labels, are disclosed.

1 . A method of specifically binding a moiety to a target, comprising:
 providing a morpholino ligand that is coupled to a moiety, the morpholino ligand comprising Formula I that specifically binds a target, wherein Formula I is:   
       
         
           
           
               
               
           
         
       
       Base is any natural or non-natural base, and n is an integer between 2 and 200; and
 contacting the target with the identified morpholino ligand coupled to the moiety, wherein the morpholino ligand specifically binds the target via non Watson-Crick binding. 
 
     
     
         2 . The method of  claim 1 , wherein the target is a protein. 
     
     
         3 . The method of  claim 2 , wherein the protein is located on the surface of a cell. 
     
     
         4 . The method of  claim 1 , wherein the moiety is a therapeutic, a label, or a marker. 
     
     
         5 . The method of  claim 4 , wherein the label comprises a fluorescent molecule. 
     
     
         6 . The method of  claim 1 , wherein the identified morpholino ligand is coupled to the moiety with a cleavable linker. 
     
     
         7 . The method of  claim 6 , wherein the cleavable linker is enzymatically cleavable. 
     
     
         8 . The method of  claim 1 , wherein the identified morpholino ligand binds the target with a binding constant of greater than 1×10 6 . 
     
     
         9 . The method of  claim 1 , wherein Base is selected from adenine, cytosine, guanine, and thymine. 
     
     
         10 . The method of  claim 1 , wherein n is an integer selected from the group consisting of: greater than 10, greater than 25, and greater than 50. 
     
     
         11 . The method of  claim 1 , wherein prior to the providing step, the method further comprises identifying the morpholino ligand by screening a library of morpholino oliogomers against the target. 
     
     
         12 . The method of  claim 11 , further comprising reverse transcribing an RNAoliogmer that is complimentary the identified morpholino ligand. 
     
     
         13 . A drug delivery system comprising:
 a drug coupled to a morpholino ligand comprising Formula I that specifically binds a target, wherein Formula I is:   
       
         
           
           
               
               
           
         
       
       Base is any natural or non-natural base, and n is an integer between 2 and 200, wherein the morpholino ligand specifically binds the target via non Watson-Crick binding. 
     
     
         14 . The drug delivery system of  claim 13 , wherein the target is a protein. 
     
     
         15 . The drug delivery system of  claim 14 , wherein the protein is located on the surface of a cell. 
     
     
         16 . The drug delivery system of  claim 13 , wherein the drug is a chemotherapeutic, an analgesic, or an anti-inflammatory. 
     
     
         16 . A labeling system comprising:
 a label coupled to a morpholino ligand comprising Formula I that specifically binds a target, wherein Formula I is:   
       
         
           
           
               
               
           
         
       
       Base is any natural or non-natural base, and n is an integer between 2 and 200, wherein the morpholino ligand specifically binds the target via non Watson-Crick binding. 
     
     
         18 . The label system of claim  17 , wherein the target is a protein. 
     
     
         19 . The label system of  claim 18 , wherein the protein is located on the surface of a cell. 
     
     
         20 . The label system of claim  17 , wherein the label is a fluorescent label, a quantum dot, or a radiopaque marker.